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From cell to tissue dynamics?

• M. Basan
• A. Basu
• A. Callan-Jones
• J.F. Joanny
• F. Julicher
• K. Kruse
• T. Risler
• G.Salbreux
• K. Sekimoto
• R. Voituriez

• C. Sykes
• E. Paluch
• P. Pullarkat

• M. Bornens
• X. Sastres
• J.P. Henry
• E. Karatekim

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Fibroblast Fragments Depolymerized Microtubules
E. Paluch et al, E.480 Bornens et al, 1988
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Filament array in lamellipodia
Arp 2/3
(T. Svitkina and G.G. Borisy, 1999 Blanchoin et
al. Pantaloni et al., 2000, Ishiwata et al 2000)
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Actin-based motility
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MYOSIN
(R. Vale)
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Muscles Actin and Myosin Filaments
titin
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Conserved quantities, Broken symmetries

• Actin (monomerpolymer)
• Myosin (bound, unbound)
• Momentum (force)
• Polarization

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Harvard Choice P.C. Martin et al
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Conservation laws
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Dissipative
Reactive
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A. Simha, S. Ramaswamy T. Liverpool, C.
Marchetti, H. Chaté
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K. Takiguchi,1991 G. H. Koenderink 2006
F. Nedelec et al 1997, K. Kruse, F. Jülicher,
2000, T. Liverpool, C. Marchetti 2002, I.
Aranson2005, B. Mulder et al 2005
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Nematic Hydrodynamics(F.M. Leslie, F. Brochard,
P.G. de Gennes, P. Pieranski, E. Guyon)
z
x
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Spontaneous Frederiks transition
R. Voituriez
V
H
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Remains to be seen!
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L. Giomi, C. Marchetti, J.F. Joanny, J.P.
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Topological Singularities
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Spontaneously moving topological singularity
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State Diagram
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EXPERIMENT(François Nedelec et al)
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Allow for density variationd2
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R. Goldstein B. subtilis
S. Ramaswamy, G. Menon et al
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Fluctuations?
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Thermal noise
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Non thermal fluctuations
Long time limit
Always unstable at long wavelength!
Traveling waves
M. Sheetz, H.G. Dobereiner
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Particle (Vesicle), Diffusion
Gel regime non thermal noise important Fluid
regime nematic coupling important
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Short time F. MacKintosh
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diffusive
balistic
F. MacKintosh
diffusive
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New material Science

• Transitions toward moving sates
• Ramaswamy waves
• Unconventional diffusion
• Long wavelength unstable
• Similar to bacterial motion, flocks etc

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Questions

• Shape (profile)
• Relation thickness/force/velocity and flow
• Substrate, membrane tension
• What determines Length?
• A. Verkhovsky symmetry breaking?

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Leading Edge
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Leading edge and membrane dynamics
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Steady motion
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Leading edge
Threshold
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Thin slab
x
h
-L/2
L/2
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Free ends
Screening!
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Lamellipodium shape and motion?
v
h
x
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A. Verkhovsky et al
In most cases d L
fcell
d
T. Betz
Keratocyte
Growth cone
Stick-Slip!
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What determines Length?
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Fragment
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Fibroblast Fragments Depolymerized Microtubules
E. Paluch et al, E.480 Bornens et al, 1988
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Fibroblast Fragments Depolymerized Microtubules
E. Paluch et al, E.480 Bornens et al, 1988
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Actin Kinase Rho Kinase
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P. Pullarkat, K. Jacobson
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Cortical Actin?
z
T
e
x
Spherical symmetryThreshold!
Intrinsically unstable!
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Pramod Pullarkat
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Activity parameter
Frequency
Calcium sensitivity
Activity Parameter
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Frequency
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Stability of an active Shell
Cell oscillations M. Bornens et al, P.
Pullarkat, K. Jacobsen
Mitosis?
D. Bray, J. Spudich et al
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Tissue Dynamics
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4) Metastatic Inefficiency
Cameron et al., Cancer Research (2000)
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Measurement of Active Tissue Homeostatic Pressure
Numbers?
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Stationary State
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Tissue Fight for Space
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3) Tumor Growth Dynamicsa) Compartment
Competition

• Force balance

• Constitutive eqns

(Liquid limit )
Highest Stationary pressure wins again!
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4) Metastatic Inefficiency

• Surface tension for at tumor boundary

If ? const
Critical Radius!
 Benign  steady state 
If ? ? faster than r
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How do you reach the critical radius?
Small tumors are monoclonal
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Nutrition/Signalization millimeter size Steady
State
Duplicating cells
Migrating cells
Necrosed cells
Stability versus Angiogenesis?
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Find?

• rc a few cell diameter
• Very sensitive on ?
• Preferential nucleation at rigid interfaces
• Seed and soil (Stephen Paget 1889)
• Papillomas virus
• But many other steps

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Messages

• Quantitative cell dynamics
• Signalization, Fluctuations
• Axones, synapses and Alzheimer
• Tissue dynamics new concepts, new experiments
• Much to do!